1887

Abstract

The early protein P35 from the baculovirus nucleopolyhedrovirus is a direct inhibitor of caspases and can block apoptosis in a wide variety of systems. In addition, it has been linked to the regulation of viral gene expression, shut-down of protein synthesis in infected insect cells and malignant transformation of mouse fibroblasts. By yeast-two-hybrid screening we identified the RPB11a subunit of human RNA polymerase II as an interaction partner of P35. Specificity of the interaction was confirmed by affinity blotting. By immunocytology, P35 was in part found in the nucleus of transfected cells. Homology searches further revealed that P35 has structural similarity with RPB3, the subunit of RNA polymerase II that has been demonstrated to interact directly with RPB11a. When transfected into human colon carcinoma cells, P35 was able to enhance the activity of E-cadherin and -actin promoters by about a factor of two as measured by luciferase reporter assay. P35 and hRPB11a together enhanced the E-cadherin activity about three- to fourfold. These data suggest an additional role for P35 in the regulation of cellular transcription.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19395-0
2003-11-01
2019-12-06
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/11/vir843011.html?itemId=/content/journal/jgv/10.1099/vir.0.19395-0&mimeType=html&fmt=ahah

References

  1. Acker, J., de Graaff, M., Cheynel, I., Khazak, V., Kedinger, C. & Vigneron, M. ( 1997; ). Interactions between the human RNA polymerase II subunits. J Biol Chem 272, 16815–16821.[CrossRef]
    [Google Scholar]
  2. Barry, M. & McFadden, G. ( 1998; ). Apoptosis regulators from DNA viruses. Curr Opin Immunol 10, 422–430.[CrossRef]
    [Google Scholar]
  3. Blanar, M. A. & Rutter, W. J. ( 1992; ). Interaction cloning: identification of a helix–loop–helix zipper protein that interacts with c-Fos. Science 256, 1014–1018.[CrossRef]
    [Google Scholar]
  4. Bruno, T., Leonetti, C., Aloe, S., Iacobini, C., Floridi, A., Di Tondo, U., Punturieri, A. & Fanciulli, M. ( 1998; ). Levels of expression of hRPB11, a core subassembly subunit of human RNA polymerase II, affect doxorubicin sensitivity and cellular differentiation. FEBS Lett 427, 241–246.[CrossRef]
    [Google Scholar]
  5. Bump, N. J., Hackett, M., Hugunin, M. & 12 other authors ( 1995; ). Inhibition of ICE family proteases by antiapoptotic protein p35. Science 269, 1885–1888.[CrossRef]
    [Google Scholar]
  6. Cheong, J. H., Yi, M., Lin, Y. & Murakami, S. ( 1995; ). Human RPB5, a subunit shared by eukaryotic nuclear RNA polymerases, binds human hepatitis B virus X protein and may play a role in X transactivation. EMBO J 14, 143–150.
    [Google Scholar]
  7. Choder, M. & Young, R. A. ( 1993; ). A portion of RNA polymerase II molecules has a component essential for stress responses and stress survival. Mol Cell Biol 13, 6984–6991.
    [Google Scholar]
  8. Clem, R. J. ( 2001; ). Baculoviruses and apoptosis: the good, the bad, and the ugly. Cell Death Differ 8, 137–143.[CrossRef]
    [Google Scholar]
  9. Clem, R. J. & Miller, L. K. ( 1993; ). Apoptosis reduces both the in vitro replication and the in vivo infectivity of a baculovirus. J Virol 67, 3730–3738.
    [Google Scholar]
  10. Clem, R. J. & Miller, L. K. ( 1994; ). Control of programmed cell death by the baculovirus genes p35 and iap. Mol Cell Biol 14, 5212–5222.
    [Google Scholar]
  11. Clem, R. J., Fechheimer, M. & Miller, L. K. ( 1991; ). Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science 254, 1388–1390.[CrossRef]
    [Google Scholar]
  12. Cramer, P., Bushnell, D. A., Fu, J. & 7 other authors ( 2000; ). Architecture of RNA polymerase II and implications for the transcription mechanism. Science 288, 640–649.[CrossRef]
    [Google Scholar]
  13. Du, X. & Thiem, S. M. ( 1997; ). Responses of insect cells to baculovirus infection: protein synthesis shutdown and apoptosis. J Virol 71, 7866–7872.
    [Google Scholar]
  14. Du, Q., Lehavi, D., Faktor, O., Qi, Y. & Chejanovsky, N. ( 1999; ). Isolation of an apoptosis suppressor gene of the Spodoptera littoralis nucleopolyhedrovirus. J Virol 73, 1278–1285.
    [Google Scholar]
  15. Earnshaw, W. C., Martins, L. M. & Kaufmann, S. H. ( 1999; ). Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68, 383–424.[CrossRef]
    [Google Scholar]
  16. Everett, H. & McFadden, G. ( 1999; ). Apoptosis: an innate immune response to virus infection. Trends Microbiol 7, 160–165.[CrossRef]
    [Google Scholar]
  17. Grandemange, S., Schaller, S., Yamano, S., Du, Manoir. S., Shpakovski, G. V., Mattei, M. G., Kedinger, C. & Vigneron, M. ( 2001; ). A human RNA polymerase II subunit is encoded by a recently generated multigene family. BMC Mol Biol 2, 14.[CrossRef]
    [Google Scholar]
  18. Gyuris, J., Golemis, E., Chertkov, H. & Brent, R. ( 1993; ). Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell 75, 791–803.[CrossRef]
    [Google Scholar]
  19. Hershberger, P. A., LaCount, D. J. & Friesen, P. D. ( 1994; ). The apoptotic suppressor P35 is required early during baculovirus replication and is targeted to the cytosol of infected cells. J Virol 68, 3467–3477.
    [Google Scholar]
  20. Ishiguro, A., Kimura, M., Yasui, K., Iwata, A., Ueda, S. & Ishihama, A. ( 1998; ). Two large subunits of the fission yeast RNA polymerase II provide platforms for the assembly of small subunits. J Mol Biol 279, 703–712.[CrossRef]
    [Google Scholar]
  21. Kamita, S. G., Majima, K. & Maeda, S. ( 1993; ). Identification and characterization of the p35 gene of Bombyx mori nuclear polyhedrosis virus that prevents virus-induced apoptosis. J Virol 67, 455–463.
    [Google Scholar]
  22. LaCount, D. J., Hanson, S. F., Schneider, C. L. & Friesen, P. D. ( 2000; ). Caspase inhibitor p35 and inhibitor of apoptosis Op-IAP block in vivo proteolytic activation of an effector caspase at different steps. J Biol Chem 275, 15657–15664.[CrossRef]
    [Google Scholar]
  23. Langelier, M. F., Forget, D., Rojas, A., Porlier, Y., Burton, Z. F. & Coulombe, B. ( 2001; ). Structural and functional interactions of transcription factor (TF) IIA with TFIIE and TFIIF in transcription initiation by RNA polymerase II. J Biol Chem 276, 38652–38657.[CrossRef]
    [Google Scholar]
  24. Miller, L. K. ( 1997; ). Baculovirus interaction with host apoptotic pathways. J Cell Physiol 173, 178–182.[CrossRef]
    [Google Scholar]
  25. Mizushima, S. & Nagat, S. ( 1990; ). pEF-BOS, a powerful mammalian expression vector. Nucleic Acids Res 18, 5322.[CrossRef]
    [Google Scholar]
  26. Morishima, N., Okano, K., Shibata, T. & Maeda, S. ( 1998; ). Homologous p35 proteins of baculoviruses show distinctive anti-apoptotic activities which correlate with the apoptosis-inducing activity of each virus. FEBS Lett 427, 144–148.[CrossRef]
    [Google Scholar]
  27. Newton, K., Harris, A. W., Bath, M. L., Smith, K. C. & Strasser, A. ( 1998; ). A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J 17, 706–718.[CrossRef]
    [Google Scholar]
  28. Ooi, B. G. & Miller, L. K. ( 1988; ). Regulation of host RNA levels during baculovirus infection. Virology 166, 515–523.[CrossRef]
    [Google Scholar]
  29. Resnicoff, M., Valentinis, B., Herbert, D., Abraham, D., Friesen, P. D., Alnemri, E. S. & Baserga, R. ( 1998; ). The baculovirus anti-apoptotic p35 protein promotes transformation of mouse embryo fibroblasts. J Biol Chem 273, 10376–10380.[CrossRef]
    [Google Scholar]
  30. Sah, N. K., Taneja, T. K., Pathak, N., Begum, R., Athar, M. & Hasnain, S. E. ( 1999; ). The baculovirus anti-apoptotic p35 gene also functions via an oxidant-dependent pathway. Proc Natl Acad Sci U S A 96, 4838–4843.[CrossRef]
    [Google Scholar]
  31. Schaller, S., Grandemange, S., Shpakovski, G. V., Golemis, E. A., Kedinger, C. & Vigneron, M. ( 1999; ). Interactions between the full complement of human RNA polymerase II subunits. FEBS Lett 461, 253–257.[CrossRef]
    [Google Scholar]
  32. Schwarze, S. R., Ho, A., Vocero-Akbani, A. & Dowdy, S. F. ( 1999; ). In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285, 1569–1572.[CrossRef]
    [Google Scholar]
  33. Tan Q. , Linask, K. L., Ebright, R. H. & Woychik, N. A. ( 2000; ). Activation mutants in yeast RNA polymerase II subunit RPB3 provide evidence for a structurally conserved surface required for activation in eukaryotes and bacteria. Genes Dev 14, 339–348.
    [Google Scholar]
  34. Thornberry, N. A., Rano, T. A., Peterson, E. P. & 9 other authors ( 1997; ). A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 272, 17907–17911.[CrossRef]
    [Google Scholar]
  35. Vier, J., Furmann, C. & Hacker, G. ( 2000; ). Baculovirus P35 protein does not inhibit caspase-9 in a cell-free system of apoptosis. Biochem Biophys Res Commun 276, 855–861.[CrossRef]
    [Google Scholar]
  36. Xu, G., Rich, R. L., Steegborn, C., Min, T., Huang, Y., Myszk, D. G. & Wu, H. ( 2003; ). Mutational analyses of the p35–caspase interaction. A bowstring kinetic model of caspase inhibition by p35. J Biol Chem 278, 5455–5461.[CrossRef]
    [Google Scholar]
  37. Zoog, S. J., Bertin, J. & Friesen, P. D. ( 1999; ). Caspase inhibition by baculovirus P35 requires interaction between the reactive site loop and the β-sheet core. J Biol Chem 274, 25995–26002.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19395-0
Loading
/content/journal/jgv/10.1099/vir.0.19395-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error